Small hydrophobic molecules such as steroid hormones and activated vitamins A and D control various biological phenomena, including growth, development, metabolism, and homeostasis, by binding to an activating specific nuclear receptors. Retinoids are natural and synthetic analogues of retinoic acid, an active metabolite of vitamin A, and are specific modulators of cell proliferation, differentiation, and morphogenesis in vertebrates. Modern medicinal chemistry of retinoids started in the 1970s (Journal of Medicinal Chemistry, 2005, 48:5875-5882 and references cited therein). One class of synthetic retinoids are derivatives of polyenecarboxylic acids or aromatic carboxylic acids which consists of three parts, that is, the hydrophobic aromatic ring, benzoic acid moiety, and the linking group between them. Retinoid therapy using synthetic retinoids has already been realized in the field of dermatology and oncology. The synthetic retinoids, such as adapalene (compound 1) has been proven to be clinically useful in the treatment of acne and psoriasis.
Similar to adapalene, a number of other active compounds such as compound 2 (Journal of Medicinal Chemistry, 2003, 46:909-912 with 1-adamantyl radical in the molecules also have therapeutic activity, including cancer chemopreventive effect. The known synthetic methods capable of producing these compounds employ 1-adamantanol as the starting material. However, this process generates disubstituted (1,2 or 1,3) adamantane as byproduct. After fine tuning the process, the disubstituted adamantane becomes the major product.
